dbSNP rs369520416: ELP5:p.Arg53Ser (chr17-7252967-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_203414.3(ELP5):c.157C>A(p.Arg53Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R53C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ELP5
NM_203414.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.937

Variant links:

Genes affected

ELP5 (HGNC:30617): (elongator acetyltransferase complex subunit 5) Predicted to contribute to tRNA binding activity. Predicted to be involved in positive regulation of cell migration and tRNA modification. Located in cytosol and nucleoplasm. Part of elongator holoenzyme complex. [provided by Alliance of Genome Resources, Apr 2022]

ELP5 links:

ENSG00000262302 (HGNC:):

ENSG00000262302 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36599165).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELP5	NM_203414.3 link	c.157C>A	p.Arg53Ser	missense_variant	Exon 3 of 8	ENST00000396628.7	NP_981959.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELP5	ENST00000396628.7 link	c.157C>A	p.Arg53Ser	missense_variant	Exon 3 of 8	1	NM_203414.3	ENSP00000379869.3		Q8TE02
ENSG00000262302	ENST00000577138.1 link	n.224-5624G>T		intron_variant	Intron 1 of 3	3		ENSP00000460571.1		I3L3M4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.74

BayesDel_addAF

Uncertain

0.054

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.029

.;.;T;.;.;T;T;.;T;.

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.84

T;T;T;.;T;.;T;.;.;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.37

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.70

MutationAssessor

Uncertain

2.6

.;.;M;M;M;M;.;M;M;M

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.8

.;.;N;.;D;N;.;.;N;.

REVEL

Benign

0.19

Sift

Benign

0.12

.;.;T;.;T;T;.;.;T;.

Sift4G

Pathogenic

0.0

D;D;T;D;D;T;D;D;T;D

Polyphen

1.0, 1.0

.;.;D;D;D;D;.;D;D;D

Vest4

0.69, 0.72, 0.69

MutPred

0.57

Gain of glycosylation at R69 (P = 0.0255);Gain of glycosylation at R69 (P = 0.0255);Gain of glycosylation at R69 (P = 0.0255);Gain of glycosylation at R69 (P = 0.0255);Gain of glycosylation at R69 (P = 0.0255);Gain of glycosylation at R69 (P = 0.0255);Gain of glycosylation at R69 (P = 0.0255);Gain of glycosylation at R69 (P = 0.0255);Gain of glycosylation at R69 (P = 0.0255);Gain of glycosylation at R69 (P = 0.0255);

MVP

0.64

MPC

0.65

ClinPred

0.95

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.32

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over